Host defense peptide mimicking poly-β-peptides with fast, potent and broad spectrum antibacterial activities

Microbial infections have always been serious challenges to human health considering that antibiotics almost inevitably induce microbial resistance. Therefore, it is urgent to develop a new antibacterial agent that is active against drug-resistant bacteria and is less susceptible to microbial resistance. In this work, a series of host defense peptide (HDP) mimicking antibacterial poly-β-peptides were synthesized, characterized and evaluated for their biological activities. The best poly-β-peptide within this study (20 : 80 Bu : DM) displays potent and broad spectrum antibacterial activity against antibiotic-resistant super bugs and low toxicity toward mammalian cells. Moreover, these poly-β-peptides are bactericidal and kill bacteria very fast within 5 min. An antimicrobial resistance test demonstrated that bacteria develop no resistance toward the selected poly-β-peptides even over 1000 generations. Our studies demonstrate that random copolymers of heterochiral poly-β-peptides, without the need for defined secondary structures, can mimic the antimicrobial HDP. These results imply the potential application of these poly-β-peptides as new antimicrobial agents to tackle drug resistant antimicrobial infections.